The present invention relates generally to bioanalytical testing procedures to aid in the diagnosis of cancer and to evaluate therapeutic treatment by antineoplastons. More particularly, the invention relates to a quantitative determination of antineoplaston levels in physiological tissues, particularly plasma and urine.
Investigations into the presence of physiologically or pathologically active peptides in various physiological tissues have been ongoing for the past 80 years. Biologically active polypeptides have been isolated from mammalian urine which have demonstrated hormone-like activity or regulation of biological function. Examples of biologically active polypeptide compositions isolated from urine include growth factors, pituitary hormones, and kinins.
The practically infinite variety of peptides that can be formed by the combination of the twenty common amino acids has prompted many investigators to suggest that peptides may constitute a system carrying information from cell to cell and organ to organ. Following this view on the regulatory significance of peptides, researchers have isolated urinary peptides which exert an influence on blood pressure, behavior modification, cardiovascular regulation, and smooth muscle activity.
Accordingly, it has been considered by a number of researchers that neoplastic growth may be controlled by naturally occurring biochemical defense mechanisms. The immunological process has most often been attributed with antineoplastic activity (see for example, Aoki et al, Prog. Exp. Tumor Res., 19:23, 1974). There are however, other possible mechanisms.
It has been suggested that neoplasia is a disease of cell differentiation. Given the large number of differentiating cells and assuming the possibility of error in the program for differentiation, groups of abnormally growing cells can often arise under the influence of carcinogenic factors. Without a reliable mechanism for "normalizing" such erroneously developed cells, the organisms would not live very long. Such a mechanism should be able to correct the growth of newly developed neoplastic cells and direct them into normal differentiation pathways. It is Applicant's belief that peptides are ideal compounds to function as information-carrying molecules regulating cell differentiation.
In recent years, Applicant has described a number of medium-sized peptides derived from human urine, which demonstrate inhibition of DNA synthesis and mitosis in cultures of various neoplastic cells without significant inhibition of normal cell replication [see Burzynski, Physiol. Chem. Phys., 5:437 (1973); Burzynski et al, Fed. Proc., 32:766 (1973); Burzynski et al, Physiol. Chem. Phys. 8:13 (1976); Burzynski et al, Fed. Proc. 35:623 (1976); Gross et al, Physiol. Chem. Phys., 8:161 (1976); Gross et al, Clin. Chem. 23:148 (1977); Burzynski, Physiol. Chem. Phys., 8:275 (1976); and Burzynski et al, Physiol. Chem. Phys. 9:485 (1977)]. More recently, Applicant has purified, isolated and characterized certain low molecular weight peptide fractions, peptides and amino acid derivatives isolated from urine which exhibit impressive antineoplastic activity [see U.S. patent application Ser. No. 279,728, filed July 2, 1981, entitled "Purified Antineoplaston Fractions and Methods of Treating Neoplastic Disease" and copending application, Ser. No. 330,383 filed Dec. 15, 1981, a continuation-in-part application of the above-referenced application Ser. No. 279,728].
The active compounds, but heretofore unidentified discrete compounds, from these fractions have been given the working name "antineoplastons". Applicant has defined antineoplastons as substances produced by a living organism that protect it against development of neoplastic growth by a nonimmunological process and that do not significantly inhibit the growth of normal tissues. In particular, Applicant has elucidated antineoplastons which are chemically classified as peptides, amino acid derivatives or hydrolysis products thereof, although he makes no representations that antineoplastons are restricted to this chemical class.
Applicant has demonstrated through extensive clinical evaluation that the antineoplaston fractions and peptides referenced above are useful in the treatment of human neoplastic disease. To date, Applicant has established a complete remission rate of about 45% and overall improvement in 93% of patients with advanced malignant neoplastic disease treated with antineoplaston fraction A2.
According to Applicant, antineoplastons, in general, offer a unique biological mechanism to combat cancer. The mechanism is viewed as a repair of young or developing cancer cells to reinstitute a more normal way of development. Research on the part of the Applicant has indicated that antineoplastons are present in the tissues and body fluids of healthy people, while people with cancer exhibit an aberrant concentration of antineoplaston for any given tissue relative to the concentration associated with healthy persons. Consequently, it is reasoned by Applicant, that the antineoplastons offer a defense or metabolic correction mechanism to protect individuals from the thousands of carcinogenic factors present in the environment which can trigger the growth of cancer.